GW researcher to help HIV patients better understand treatments for cardiovascular issues

In 1980, men and women who were diagnosed with the human immunodeficiency virus (HIV) had little to no hope of living long, full lives. Thanks to advances in science and medicine, this is no longer the case. HIV patients now live a near-normal lifespan. However, as patients live longer, new medical issues arise. Michael I. Bukrinsky, M.D., Ph.D., professor of microbiology, immunology, and tropical medicine and professor of biochemistry and molecular biology at the George Washington University School of Medicine and Health Sciences, saw that cardiovascular disease was becoming a major clinical problem in HIV patients. The National Institutes of Health (NIH) and the National Heart, Lung, and Blood Institute awarded him a grant to study the issue further. His research on this topic is in its third year, and in August, he received a supplement of $156,292 to continue his efforts to find a way to help HIV patients better understand treatments for health issues that may arise as they age.

His project, titled "HIV Disease and Impairment of High Density Lipoprotein Metabolism," will look into the mechanisms of atherosclerosis in HIV-infected patients. One question that will be addressed is whether, as many believe, cardiovascular issues in HIV patients are due to the adverse effects of pro-longed use of toxic anti-HIV drugs. Bukrinsky believes that while drugs may contribute to this problem, HIV infection itself may also be a significant factor.

"The belief has been, that the reason for cardiovascular issues was not HIV itself, but drugs used to treat HIV," said Bukrinsky. "We are trying to prove that though drugs may contribute to this problem, HIV itself is actually a very significant risk factor. These two factors work together to infuse this atherosclerotic change in patients."

Bukrinsky has been studying the effects of HIV infection on metabolism and the function of high-density lipoprotein (HDL), in hopes of finding a way to target and treat cardiovascular disease in these patients. The supplemental funding will be used to establish an animal model that will recreate the events researchers think are happening in HIV patients. Bukrinsky believes that cells infected with HIV are secreting viral protein called Nef into the blood stream that then cause other, uninfected cells to produce lower HDL levels. To study whether this is occurring, the transgenic mice will produce this protein from their cells, which will enter their bloodstream. Bukrinsky and his research team will then study what affect this has on HDL to either prove or disprove their hypothesis.

"If we see these mice have low levels of HDL, compared to the control group of mice, it will prove that Nef can influence HDL levels," said Bukrinsky. "If we prove our hypothesis, we find the mechanisms of how HIV does that and we will be able to treat the condition. The direct application would be drugs that target Nef and prevent its effects on this HDL metabolism. That is the ultimate goal."